Nuclear factor kappa B p65 complex (NF-κB p65)

The p65-containing NF-κB complex, most commonly the p50/p65 heterodimer, is a central transcription factor that regulates the expression of genes involved in immunity, inflammation, and cell survival [1, 5]. In its inactive state, the complex is sequestered in the cytoplasm by inhibitor of κB (IκB) proteins [1, 11]. Upon activation by stimuli such as pro-inflammatory cytokines (e.g., TNF-α) or pathogen-associated molecular patterns, the IκB kinase (IKK) complex phosphorylates IκB, leading to its proteasomal degradation and the subsequent nuclear translocation of the p65 complex [1, 8]. Once in the nucleus, the p65 subunit uses its transactivation domain to recruit co-activators and initiate the transcription of target genes like IL-6 and TNF-α [14, 15]. Dysregulation of this pathway is strongly linked to chronic inflammatory conditions, autoimmune diseases, and various cancers, where it promotes tumor cell proliferation and resistance to apoptosis [1, 6]. Therapeutic strategies targeting this complex include proteasome inhibitors like bortezomib, which prevent IκB degradation, and glucocorticoids that induce IκB expression and directly interfere with p65 activity [8, 13]. Emerging research also focuses on small molecules and peptides that directly block p65 DNA binding or its interaction with transcriptional co-regulators [9, 13].

Other names

RELATranscription factor p65NFKB3Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3p65 subunit of NF-kappaBp50/p65 heterodimer

Inhibition of the NF-κB signaling pathway by preventing IκB degradation, blocking nuclear translocation of p65, or interfering with p65 DNA binding and transactivation.